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The shanty boat people of Island No. 21 in the Mississippi River know little about life in towns. Following the wedding of Ernie Holley and Pearl Elliott, a "land girl" from Tennessee, Slade, a slovenly fish buyer from the outside, is knocked into the river by Ernie for kissing his bride against his wishes. When the police come, Ernie swims away and thus upsets the plans of his father Newt to serenade the couple with the song "St. Louis Blues" on his "contraption," an assortment of connected musical instruments, in a toast to his future first "grandbaby." Slade turns up unharmed, but Ernie, unaware, becomes a sailor and visits six countries before his return six months later. As Newt waits to serenade them, Ernie and Pearl argue because he announces that he plans to leave again to work in Aruba. Angered that Pearl questions the husband's right to make decisions, Ernie leaves in a rowboat. Pearl immediately goes off with Warfield Scott, a philandering photographer who offers her a job in his New Orleans studio. When Ernie returns, he follows them vowing to break both their necks. In New Orleans, after Pearl sees Scott's squalid studio, she finds work as a dishwasher in the Cafe Creole to repay Scott for his expenditures. Ernie arrives and throws Scott through a picture, and then goes off with sailors to work in Havana when he cannot find Pearl. Two weeks later, Newt arrives and throws Scott through another picture, and after he plays his "contraption" at the Cafe Creole, Newt teams up with Pearl and Chick Bean, a down-on-his-luck singer who has fallen in love with Pearl. After Ernie returns and sees Scott and Pearl together, he starts a brawl which nearly destroys the cafe. Because of Ernie's temper, Pearl decides to go with Chick to Chicago. Back home, Ernie agrees to marry Leota Long, who earlier jealously snubbed Pearl and now, at the wedding, wears the kimono from Genoa that Ernie once gave Pearl. Pearl returns for the kimono and fights Leota, who during a violent rainstorm, cuts the ropes binding the Holley houseboat to the island. After Newt and Ernie navigate to a sandbar and Newt locks the feuding couple inside the houseboat, they finally kiss, and he happily serenades them with the "St. Louis Blues."